Synthesis of phthalide derivatives and evaluation on their antiplatelet aggregation and antioxidant activities

Abstract

As part of our continuing efforts to discover structurally interesting bioactive phthalide derivatives, 23 of them with a structure incorporating thiophen or halogens were designed and synthesized, 17 of which are previously unreported. In vitro antiplatelet aggregation activity screening showed that 14b could significantly inhibit platelet aggregation induced by arachidonic acid, compared with edaravone (p < 0.01). Meanwhile, oxidative damage models using SH-SY5Y and PC12 cells induced by H₂O₂ were built to evaluate the antioxidant activity of the phthalide derivatives. In SH-SY5Y cells, compared with aspirin, 1a significantly increased the relative cell survival rate (p < 0.05). Compared with edaravone, 1a (p < 0.01) and 15b (p < 0.05) significantly increased the relative cell survival rate. In PC12 cells, 1a (p < 0.01), 15b (p < 0.01), and 12a (p < 0.05) remarkably increased the cell survival rate compared with edaravone. The present study identified lead structures to develop potential anti-ischemic stroke agents.

Graphical Abstract

Keywords:

• Phthalide derivative
• antiplatelet aggregation
• antioxidation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by the Shanghai Municipal Commission of Health and Family Planning [grant number ZY3-CCCX-3-5001], the Science and Technology Commission of Shanghai Municipality [grant numbers 14401901400, 15DZ2292000], the Expenditure Budget Program of Shanghai Municipal Education Commission [grant number 2016YSN24], and Xinglin Young Talent Program of Shanghai University of Traditional Chinese Medicine.